The SCOR in Thrombosis is designed to elucidate the role of von Willebrand factor, platelets and the vessel wall in arterial thrombosis. To accomplish this broad objective we have established a unique colony of pigs with homozygous von Willebrand's disease (VMD) that have undetectable levels of von Willebrand factor in plasma and platelets. These animals are resistant to coronary artery thrombosis but develop thrombosis when platelet VWF is restored. We plan to extend these studies to intracellular platelet messengers in order to determine the role of intraplatelet events in aggregation and release. We also will extend studies on platelet and smooth muscle cell (SMC) mitogens that induce SMC proliferation, the hallmark of the atherosclerotic lesion on which thrombosis usually occurs. Finally, we will focus on other vessel wall constituents, namely, thrombomodulin, endothelial cell and SMC transglutaminase, perturbations of which are of potential great importance in thrombosis. These studies will be supported by 3 cores: Administrative Core, Animal Core and a Clinical Core, the latter designed to take basic research observations and apply them to clinical situations. All SCOR projects are interrelated and the total contribution of the sum effort of these studies will be greater than any individual component.